Identification of T helper type 1-like, Foxp3+ regulatory T cells in human autoimmune disease

CD4(+) CD25(high)CD127(low)/-forkhead box p3 (Foxp3)(+) regulatory T cells (T-reg cells) possess functional plasticity. Here we describe a higher frequency of T helper type 1 (T(H)1)-like, interferon-gamma (IFN-gamma)-secreting Foxp3(+) T cells in untreated subjects with relapsing remitting multiple sclerosis (RRMS) as compared to healthy control individuals. In subjects treated with IFN-beta, the frequency of IFN-gamma(+) Foxp3(+) T cells is similar to that in healthy control subjects. In vitro, human T-reg cells from healthy subjects acquire a T(H)1-like phenotype when cultured in the presence of interleukin-12 (IL-12). T(H)1-like T-reg cells show reduced suppressive activity in vitro, which can partially be reversed by IFN-gamma-specific antibodies or by removal of IL-12.